Publications by authors named "Richard Evans"

432 Publications

Team Evans and Watkins: Excitatory Amino Acid Research at Bristol 1973-1981.

Neuropharmacology 2021 Aug 26:108768. Epub 2021 Aug 26.

Formerly of: The Department of Pharmacology, The Medical School, The University of Bristol, University Walk, Bristol, BS8 1TD, UK. Electronic address:

A series of Special Issues of Neuropharmacology celebrates the 40 anniversary of a seminal review on excitatory amino acid (EAA) receptors by two pioneers of the field - Dick Evans and Jeff Watkins. Brought together in the Department of Pharmacology at the University of Bristol in the 1970s, they forged a partnership that, through the synthetic chemistry prowess of Jeff Watkins, which provided novel agonists and antagonists for EAA receptors for Dick Evans's deft experimental studies, generated enormous insight into the multitude of actions of EAAs in the nervous system. Among many achievements from this time was not just the naming of the N-methyl-D-aspartate (NMDA) receptor, but also the demonstration of its antagonism by magnesium ions. Here, Dick and Jeff reflect upon those early halcyon days of EAA research, which, as these six Special Issues of Neuropharmacology demonstrate, is very much alive and kicking.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108768DOI Listing
August 2021

Facility-level conditions leading to higher reach: a configurational analysis of national VA weight management programming.

BMC Health Serv Res 2021 Aug 11;21(1):797. Epub 2021 Aug 11.

Veterans Affairs Center for Clinical Management Research, VA Ann Arbor Healthcare System, Michigan, Ann Arbor, USA.

Background: While the Veterans Health Administration (VHA) MOVE! weight management program is effective in helping patients lose weight and is available at every VHA medical center across the United States, reaching patients to engage them in treatment remains a challenge. Facility-based MOVE! programs vary in structures, processes of programming, and levels of reach, with no single factor explaining variation in reach. Configurational analysis, based on Boolean algebra and set theory, represents a mathematical approach to data analysis well-suited for discerning how conditions interact and identifying multiple pathways leading to the same outcome. We applied configurational analysis to identify facility-level obesity treatment program arrangements that directly linked to higher reach.

Methods: A national survey was fielded in March 2017 to elicit information about more than 75 different components of obesity treatment programming in all VHA medical centers. This survey data was linked to reach scores available through administrative data. Reach scores were calculated by dividing the total number of Veterans who are candidates for obesity treatment by the number of "new" MOVE! visits in 2017 for each program and then multiplied by 1000. Programs with the top 40 % highest reach scores (n = 51) were compared to those in the lowest 40 % (n = 51). Configurational analysis was applied to identify specific combinations of conditions linked to reach rates.

Results: One hundred twenty-seven MOVE! program representatives responded to the survey and had complete reach data. The final solution consisted of 5 distinct pathways comprising combinations of program components related to pharmacotherapy, bariatric surgery, and comprehensive lifestyle intervention; 3 of the 5 pathways depended on the size/complexity of medical center. The 5 pathways explained 78 % (40/51) of the facilities in the higher-reach group with 85 % consistency (40/47).

Conclusions: Specific combinations of facility-level conditions identified through configurational analysis uniquely distinguished facilities with higher reach from those with lower reach. Solutions demonstrated the importance of how local context plus specific program components linked together to account for a key implementation outcome. These findings will guide system recommendations about optimal program structures to maximize reach to patients who would benefit from obesity treatment such as the MOVE!

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http://dx.doi.org/10.1186/s12913-021-06774-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359110PMC
August 2021

21st century excitatory amino acid research: A Q & A with Jeff Watkins and Dick Evans.

Neuropharmacology 2021 Aug 5;198:108743. Epub 2021 Aug 5.

School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK. Electronic address:

In 1981 Jeff Watkins and Dick Evans wrote what was to become a seminal review on excitatory amino acids (EAAs) and their receptors (Watkins and Evans, 1981). Bringing together various lines of evidence dating back over several decades on: the distribution in the nervous system of putative amino acid neurotransmitters; enzymes involved in their production and metabolism; the uptake and release of amino acids; binding of EAAs to membranes; the pharmacological action of endogenous excitatory amino acids and their synthetic analogues, and notably the actions of antagonists for the excitations caused by both nerve stimulation and exogenous agonists, often using pharmacological tools developed by Jeff and his colleagues, they provided a compelling account for EAAs, especially l-glutamate, as a bona fide neurotransmitter in the nervous system. The rest, as they say, is history, but far from being consigned to history, EAA research is in rude health well into the 21st Century as this series of Special Issues of Neuropharmacology exemplifies. With EAAs and their receptors flourishing across a wide range of disciplines and clinical conditions, we enter into a dialogue with two of the most prominent and influential figures in the early days of EAA research: Jeff Watkins and Dick Evans.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108743DOI Listing
August 2021

Highly accurate protein structure prediction for the human proteome.

Nature 2021 Aug 22;596(7873):590-596. Epub 2021 Jul 22.

European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.

Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally determined structure. Here we markedly expand the structural coverage of the proteome by applying the state-of-the-art machine learning method, AlphaFold, at a scale that covers almost the entire human proteome (98.5% of human proteins). The resulting dataset covers 58% of residues with a confident prediction, of which a subset (36% of all residues) have very high confidence. We introduce several metrics developed by building on the AlphaFold model and use them to interpret the dataset, identifying strong multi-domain predictions as well as regions that are likely to be disordered. Finally, we provide some case studies to illustrate how high-quality predictions could be used to generate biological hypotheses. We are making our predictions freely available to the community and anticipate that routine large-scale and high-accuracy structure prediction will become an important tool that will allow new questions to be addressed from a structural perspective.
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http://dx.doi.org/10.1038/s41586-021-03828-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387240PMC
August 2021

Highly accurate protein structure prediction with AlphaFold.

Nature 2021 Aug 15;596(7873):583-589. Epub 2021 Jul 15.

DeepMind, London, UK.

Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort, the structures of around 100,000 unique proteins have been determined, but this represents a small fraction of the billions of known protein sequences. Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence-the structure prediction component of the 'protein folding problem'-has been an important open research problem for more than 50 years. Despite recent progress, existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14), demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm.
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http://dx.doi.org/10.1038/s41586-021-03819-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371605PMC
August 2021

What makes a molecule a pre- or a post-herbicide - how valuable are physicochemical parameters for their design?

Pest Manag Sci 2021 Jun 27. Epub 2021 Jun 27.

Richard Evans, Raleigh, NC, USA.

Pre-emergence herbicides are taken up by seeds before germination and by roots, hypocotyls, cotyledons, coleoptiles or leaves before emergence, whereas post-emergence herbicides are taken up primarily by foliage and stems. Most modern pre-emergence herbicides are lipophilic, but post-emergence herbicides may be lipophilic or hydrophilic. The metabolic conversion of herbicides to inactive or active metabolites after plant uptake is of major importance for some compound classes. Several herbicides are proherbicides as for example some acetyl-coenzyme A carboxylase (ACCase)-inhibitors. The physicochemical characteristics of proherbicides and herbicides are usually unrelated. A major role can be attributed to the site of action at a cellular level. A great number of herbicides such as photosystem II (PS II)-inhibitors, protoporphyrinogen oxidase (PPO)-inhibitors or carotenoid biosynthesis inhibitors require light for activity. Others, such as cellulose-biosynthesis and mitotic inhibitors seem to be primarily active in belowground organs. Several lipophilic barriers against the uptake of xenobiotics exist in aboveground and belowground plant parts. The relevance of these barriers needs, however, further clarification. Uptake and translocation models are valuable tools for the explanation of the potential movement of compounds. Many factors other than uptake and translocation have, however, to be considered for the design of herbicides. For post-emergence herbicides, ultraviolet (UV) light stability, stability in formulations, and mixability with other agrochemicals have to be kept in mind while, in addition to the aforementioned factors soil interaction plays a major role for pre-emergence herbicides. In our opinion, general physicochemical characteristics of pre- or post-emergence herbicides do, unfortunately not exist yet. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6535DOI Listing
June 2021

Age or frailty: What matters in oesophagectomy for cancer in the elderly?

Eur J Surg Oncol 2021 May 18. Epub 2021 May 18.

Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.ejso.2021.05.030DOI Listing
May 2021

Letter to the Editor in response to the Position statement and best practice recommendations on the imaging use of ultrasound from the European Society of Radiology ultrasound subcommittee.

Insights Imaging 2021 May 20;12(1):61. Epub 2021 May 20.

Society and College of Radiographers, London, UK.

This letter to the editor is in response to the consensus statement from the Ultrasound Subcommittee of the European Society of Radiology, the European Union of Medical Specialists (UEMS) Section of Radiology, and the European Federation of Societies for Ultrasound in Medicine and Biology. It highlights the role of the non-medical sonographer in the UK and the evidence underpinning this safe and effective practice.
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http://dx.doi.org/10.1186/s13244-021-01002-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134581PMC
May 2021

The Impact of Community Care Referral on Time to Surgery for Veterans With Carpal Tunnel Syndrome.

Med Care 2021 Jun;59(Suppl 3):S279-S285

Section of Plastic Surgery, Michigan Medicine.

Background: The US Department of Veterans Affairs (VA) enacted policies offering Veterans care in the community, aiming to improve access challenges. However, the impact of receipt of community care on wait times for Veterans receiving surgical care is poorly understood.

Objectives: To compare wait times for surgery for Veterans with carpal tunnel syndrome who receive VA care plus community care (mixed care) and those who receive care solely within the VA (VA-only).

Research Design: Retrospective cohort study.

Subjects: Veterans undergoing carpal tunnel release (CTR) between January 1, 2010 and December 31, 2016.

Measures: Our primary outcome was time from primary care physician (PCP) referral to CTR.

Results: Of the 29,242 Veterans undergoing CTR, 23,330 (79.8%) received VA-only care and 5912 (20.1%) received mixed care. Veterans receiving mixed care had significantly longer time from PCP referral to CTR (median mixed care: 378 days; median VA-only care: 176 days, P<0.001). After controlling for patient and facility covariates, mixed care was associated with a 37% increased time from PCP referral to CTR (adjusted hazard ratio, 0.63; 95% confidence interval, 0.61-0.65). Each additional service provided in the community was associated with a 23% increase in time to surgery (adjusted hazard ratio, 0.77; 95% confidence interval, 0.76-0.78).

Conclusions: VA-only care was associated with a shorter time to surgery compared with mixed care. Moreover, there were additional delays for each service received in the community. With likely increases in Veterans seeking community care, strategies must be used to identify and mitigate sources of delay through the spectrum of care between referral and definitive treatment.
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http://dx.doi.org/10.1097/MLR.0000000000001469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121165PMC
June 2021

Effectiveness of Influenza Vaccines in the HIVE household cohort over 8 years: is there evidence of indirect protection?

Clin Infect Dis 2021 May 5. Epub 2021 May 5.

University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, MI, USA.

Background: The evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (i.e. indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort.

Methods: Using longitudinal data from the HIVE cohort from 2010-11 through 2017-18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households.

Results: The pooled, direct VE against any influenza was 30.2% (14.0-43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8); and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (-6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccination coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VE was 56.4% (30.1-72.9) in low coverage, 43.2% (19.5-59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households.

Conclusion: Influenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. While there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.
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http://dx.doi.org/10.1093/cid/ciab395DOI Listing
May 2021

Executive Summary: Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report.

Chest 2021 Aug 15;160(2):595-615. Epub 2021 Apr 15.

American College of Chest Physicians, Glenview, IL.

Background: The purpose of this summary is to provide a synopsis of evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability.

Study Design And Methods: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, and Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus.

Results: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations, and 2 ungraded consensus-based statements. All evidence was of very low quality.

Interpretation: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.
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http://dx.doi.org/10.1016/j.chest.2021.03.067DOI Listing
August 2021

Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report.

Chest 2021 Aug 20;160(2):e97-e156. Epub 2021 Apr 20.

American College of Chest Physicians, Glenview, IL.

Background: The purpose of this analysis is to provide evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability.

Study Design And Methods: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. A diagnostic algorithm is provided, using supporting data from the recommendations where possible, along with expert consensus to help physicians gauge the probability of HP.

Results: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations and 2 ungraded consensus-based statements. All evidence was of very low quality.

Interpretation: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Criteria are presented to facilitate diagnosis of HP. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.
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http://dx.doi.org/10.1016/j.chest.2021.03.066DOI Listing
August 2021

Coral larval recruitment in north-western Australia predicted by regional and local conditions.

Mar Environ Res 2021 Jun 3;168:105318. Epub 2021 Apr 3.

Australian Research Council Centre of Excellence for Coral Reef Studies, James Cook University, Townsville, Queensland, 4811, Australia.

Understanding ecological processes that shape contemporary and future communities facilitates knowledge-based environmental management. In marine ecosystems, one of the most important processes is the supply of new recruits into a population. Here, we investigated spatiotemporal variability in coral recruitment at 15 reefs throughout the Dampier Archipelago, north-western Australia between 2015 and 2017 and identified the best environmental predictors for coral recruitment patterns over this period. Large differences in recruitment were observed among years with the average density of recruits increasing by 375% from 0.017 recruits cm in 2015 to 0.059 recruits cm in 2017. Despite differences in recruitment among years, the rank order of coral recruit density among reefs remained similar among years, suggesting that spatial variation in recruitment within the Dampier Archipelago is partly deterministic and predictable. The density of coral recruits was best explained by percent cover of live corals at both local (within 5 m) and meso-scales (within 15 km), water turbidity and an oceanographic model that predicted larval dispersal. The highest density of coral recruits (~0.13 recruits cm or 37 recruits per tile) occurred on reefs within sub-regions (15 km) with greater than 35% coral cover, low to moderate turbidity (KD490 < 0.2) and moderate to high modelled predictions of larval dispersal. Our results demonstrate that broad-scale larval dispersal models, when combined with local metrics of percent hard coral cover and water turbidity, can reliably predict the relative abundance of coral recruits over large geographical areas and thus can identify hotspots of recruit abundance and potential recovery following environmental disturbances; information that is essential for effective management of coral reefs.
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http://dx.doi.org/10.1016/j.marenvres.2021.105318DOI Listing
June 2021

Elderly patients have increased perioperative morbidity and mortality from oesophagectomy for oesophageal cancer: A systematic review and meta-analysis.

Eur J Surg Oncol 2021 Aug 27;47(8):1828-1835. Epub 2021 Mar 27.

Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. Electronic address:

Background: Although oesophagectomy remains technically challenging and associated with high morbidity and mortality, it is now increasingly performed in an ever-ageing population with improvement in perioperative care. However, the risks in the elderly population are poorly quantified. The study aims to review the current evidence to quantify further the postoperative risk of oesophagectomy for cancer in the elderly population compared to younger patients.

Method: A systematic literature search of PubMed, EMBASE and the Cochrane Library databases was conducted including studies reporting oesophagectomy for cancer in the elderly population. A meta-analysis was reported in accordance with the recommendations of the Cochrane Library and PRISMA guidelines. Primary outcome was overall complications and secondary outcomes were pulmonary and cardiac complications, anastomotic leaks, overall and disease-free survival.

Results: This review identified 37 studies incorporating 30,836 patients. Increasing age was significantly associated with increased rates of overall complications (OR 1.67, CI: 1.42-1.96), pulmonary complications (OR 1.87, CI: 1.48-2.35), and cardiac complications (OR: 2.22, CI: 1.95-2.53). However, there was no increased risk of anastomotic leak (OR: 0.98, CI: 0.85-1.18). Elderly patients were significantly more likely to have lower rates of 5-year overall survival (OR: 1.36, CI: 1.11-1.66) and 5-year disease-free survival (OR: 1.72, CI: 1.51-1.96).

Conclusion: Elderly patients undergoing oesophagectomy for cancer are at increased risk of overall, pulmonary and cardiac complications, irrespective of age subgroups, albeit no difference in anastomotic leaks. Therefore, they represent high-risk patients warranting implementation of preoperative pathways such as prehabilitation to improve cardiopulmonary fitness prior to surgery, although benefit of prehabilitation is yet to be proven. This information will also aid future pre-operative counselling and informed consent.
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http://dx.doi.org/10.1016/j.ejso.2021.02.030DOI Listing
August 2021

Cyberbullying Among Adolescents and Children: A Comprehensive Review of the Global Situation, Risk Factors, and Preventive Measures.

Front Public Health 2021 11;9:634909. Epub 2021 Mar 11.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cyberbullying is well-recognized as a severe public health issue which affects both adolescents and children. Most extant studies have focused on national and regional effects of cyberbullying, with few examining the global perspective of cyberbullying. This systematic review comprehensively examines the global situation, risk factors, and preventive measures taken worldwide to fight cyberbullying among adolescents and children. A systematic review of available literature was completed following PRISMA guidelines using the search themes "cyberbullying" and "adolescent or children"; the time frame was from January 1st, 2015 to December 31st, 2019. Eight academic databases pertaining to public health, and communication and psychology were consulted, namely: Web of Science, Science Direct, PubMed, Google Scholar, ProQuest, Communication & Mass Media Complete, CINAHL, and PsycArticles. Additional records identified through other sources included the references of reviews and two websites, Cyberbullying Research Center and United Nations Children's Fund. A total of 63 studies out of 2070 were included in our final review focusing on cyberbullying prevalence and risk factors. The prevalence rates of cyberbullying preparation ranged from 6.0 to 46.3%, while the rates of cyberbullying victimization ranged from 13.99 to 57.5%, based on 63 references. Verbal violence was the most common type of cyberbullying. Fourteen risk factors and three protective factors were revealed in this study. At the personal level, variables associated with cyberbullying including age, gender, online behavior, race, health condition, past experience of victimization, and impulsiveness were reviewed as risk factors. Likewise, at the situational level, parent-child relationship, interpersonal relationships, and geographical location were also reviewed in relation to cyberbullying. As for protective factors, empathy and emotional intelligence, parent-child relationship, and school climate were frequently mentioned. The prevalence rate of cyberbullying has increased significantly in the observed 5-year period, and it is imperative that researchers from low and middle income countries focus sufficient attention on cyberbullying of children and adolescents. Despite a lack of scientific intervention research on cyberbullying, the review also identified several promising strategies for its prevention from the perspectives of youths, parents and schools. More research on cyberbullying is needed, especially on the issue of cross-national cyberbullying. International cooperation, multi-pronged and systematic approaches are highly encouraged to deal with cyberbullying.
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http://dx.doi.org/10.3389/fpubh.2021.634909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006937PMC
May 2021

Emotional Attitudes of Chinese Citizens on Social Distancing During the COVID-19 Outbreak: Analysis of Social Media Data.

JMIR Med Inform 2021 Mar 16;9(3):e27079. Epub 2021 Mar 16.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

Background: Wuhan, China, the epicenter of the COVID-19 pandemic, imposed citywide lockdown measures on January 23, 2020. Neighboring cities in Hubei Province followed suit with the government enforcing social distancing measures to restrict the spread of the disease throughout the province. Few studies have examined the emotional attitudes of citizens as expressed on social media toward the imposed social distancing measures and the factors that affected their emotions.

Objective: The aim of this study was twofold. First, we aimed to detect the emotional attitudes of different groups of users on Sina Weibo toward the social distancing measures imposed by the People's Government of Hubei Province. Second, the influencing factors of their emotions, as well as the impact of the imposed measures on users' emotions, was studied.

Methods: Sina Weibo, one of China's largest social media platforms, was chosen as the primary data source. The time span of selected data was from January 21, 2020, to March 24, 2020, while analysis was completed in late June 2020. Bi-directional long short-term memory (Bi-LSTM) was used to analyze users' emotions, while logistic regression analysis was employed to explore the influence of explanatory variables on users' emotions, such as age and spatial location. Further, the moderating effects of social distancing measures on the relationship between user characteristics and users' emotions were assessed by observing the interaction effects between the measures and explanatory variables.

Results: Based on the 63,169 comments obtained, we identified six topics of discussion-(1) delaying the resumption of work and school, (2) travel restrictions, (3) traffic restrictions, (4) extending the Lunar New Year holiday, (5) closing public spaces, and (6) community containment. There was no multicollinearity in the data during statistical analysis; the Hosmer-Lemeshow goodness-of-fit was 0.24 (χ=10.34, P>.24). The main emotions shown by citizens were negative, including anger and fear. Users located in Hubei Province showed the highest amount of negative emotions in Mainland China. There are statistically significant differences in the distribution of emotional polarity between social distancing measures (χ=19,084.73, P<.001), as well as emotional polarity between genders (χ=1784.59, P<.001) and emotional polarity between spatial locations (χ=1659.67, P<.001). Compared with other types of social distancing measures, the measures of delaying the resumption of work and school or travel restrictions mainly had a positive moderating effect on public emotion, while traffic restrictions or community containment had a negative moderating effect on public emotion.

Conclusions: Findings provide a reference point for the adoption of epidemic prevention and control measures, and are considered helpful for government agencies to take timely actions to alleviate negative emotions during public health emergencies.
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http://dx.doi.org/10.2196/27079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968412PMC
March 2021

Patient and public involvement prior to trial initiation: lessons learnt for rapid partnership in the COVID-19 era.

Res Involv Engagem 2021 Mar 8;7(1):13. Epub 2021 Mar 8.

London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Patient and Public Involvement (PPI) describes the active involvement of patients and the public in the research process. Through PPI, patients and members of the public are increasingly involved in the design and conduct of clinical trials. PPI has been shown to improve the quality and relevance of research. During the COVID-19 pandemic, clinical trials have been playing a vital role in helping us find ways to prevent and treat the infection and improve our understanding of the virus. It is important that patients and the public are actively involved in deciding how COVID-19 research is carried out. Unfortunately, Research Ethics Committees in the UK have seen far less PPI for COVID-19 research studies compared with research before the pandemic. A key reason for this is that research is being designed much faster than normal and researchers may feel they do not have time to properly involve patients and the public. In this paper, we share our experiences of PPI for a COVID-19 clinical trial. We show that it is possible to rapidly involve patients and the public in COVID-19 clinical trials. We also explain how the design of the clinical trial was changed in response to feedback from public contributors. Lastly, we discuss the wider learning from this process which might be useful for researchers planning PPI activities for COVID-19 clinical trials in the future.

Background: Clinical trials are playing a critical role in the global public health response to the COVID-19 pandemic. Despite the increasing recognition of the value of PPI in clinical trials, just 22% of the COVID-19 research proposals reviewed by Research Ethics Committees in the UK at the start of the pandemic reported PPI. There is a perception that PPI might result in delays in delivering research and therefore delays in obtaining important results. In this paper, we report our experience of rapid PPI for a COVID-19 clinical trial.

Methods: RAPID-19 is a COVID-19 clinical trial which was planned to be submitted for fast-track ethics review in the United Kingdom. During the development of the trial protocol, the PPI Panel at the London School of Hygiene & Tropical Medicine Clinical Trials Unit was involved in the design of the study. The meeting with the PPI Panel lasted just over 1 h and was conducted by teleconference.

Results: Although we only had a short period of time to explore the study with the PPI Panel, we were able to gain valuable insight into how the trial would be perceived by potential trial participants. Substantive changes were made to the trial to improve the acceptability of the research without compromising the study timelines. Having access to public contributors with relevant lived experience is an important resource for a Clinical Trials Unit and is critical for rapid PPI. The move to remote working due to lockdown required virtual discussions which helped to overcome some of the barriers to organising face-to-face meetings at short notice.

Conclusions: PPI for clinical trials can be conducted in a time-efficient manner within the pressured environment of a pandemic. Involving PPI contributors at an early stage in protocol development maximised the opportunity to shape and influence the trial as well as limited potential delays which could occur if changes to the protocol had to be made at a later stage.
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http://dx.doi.org/10.1186/s40900-021-00250-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938674PMC
March 2021

Role of anti-phase boundaries in the formation of magnetic domains in magnetite thin films.

J Phys Condens Matter 2021 Apr 23;33(17). Epub 2021 Apr 23.

Department of Physics, University of York, Heslington, York, YO10 5DD, United Kingdom.

Anti-phase boundaries (APBs) are structural defects which have been shown to be responsible for the anomalous magnetic behavior observed in different nanostructures. Understanding their properties is crucial in order to use them to tune the properties of magnetic materials by growing APBs in a controlled way since their density strongly depends on the synthesis method. In this work we investigate their influence on magnetite (FeO) thin films by considering an atomistic spin model, focussing our study on the role that the exchange interactions play across the APB interface. We conclude that the main atypical features reported experimentally in this material are well described by the model we propose here, confirming the new exchange interactions created in the APB as the responsible for this deviation from bulk properties.
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http://dx.doi.org/10.1088/1361-648X/abe26cDOI Listing
April 2021

Custom Dynamic Orthoses and Physical Therapist Intervention for Bilateral Midfoot Amputation: A Case Report.

Phys Ther 2021 04;101(4)

Department of Physical Therapy and Rehabilitation Science, The University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.

Objective: Partial foot amputation is often associated with decreased mobility and function. Recent advances in custom carbon-fiber dynamic ankle-foot orthoses (CDOs) have improved gait, pain, and function following musculoskeletal trauma and can benefit individuals with partial foot amputation. However, limited information is available related to CDO use outside the military. The purpose of this case report is to describe the course of care and outcomes of a civilian provided with CDOs after bilateral transmetatarsal amputation.

Case Description: A 72-year-old man had a blood-borne bacterial infection (septicemia) of unknown origin at 68 years of age, developed limb-threatening necrosis of the hands and feet, and received bilateral transmetatarsal amputations with skin grafting. The patient initially used foam toe fillers and cushioned shoes but was functionally limited and experienced recurrent ulceration. He was fitted with bilateral CDOs 39 months after amputation and completed device-specific training with a physical therapist.

Results: After 1 week with the CDOs, ankle range of motion during gait was reduced, but greater than 40% increases were observed in bilateral ankle plantarflexor moments and ankle plantarflexion push-off power compared with the toe fillers. With additional therapist-directed training focused on gait and activity performance, ankle plantarflexor moments and plantarflexion push-off power further increased when compared with results after 1 week of CDO use. The patient reported marked improvement in quality of life with the CDOs due to improved walking ability on level and uneven terrain, marked improvement in confidence, and reduced pain.

Conclusion: This case reflects the lessons learned and outcomes of a civilian using bilateral CDOs after bilateral transmetatarsal amputation and with poor skin quality. The results from this case study suggest that carbon-fiber CDOs and focused training by a physical therapist can result in improved gait biomechanics, mobility, and quality of life.
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http://dx.doi.org/10.1093/ptj/pzab028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054777PMC
April 2021

Factors Driving Citizen Engagement With Government TikTok Accounts During the COVID-19 Pandemic: Model Development and Analysis.

J Med Internet Res 2021 02 4;23(2):e21463. Epub 2021 Feb 4.

College of Engineering, Design and Physical Sciences, Brunel University London, London, United Kingdom.

Background: During the COVID-19 pandemic, growth in citizen engagement with social media platforms has enabled public health departments to accelerate and improve health information dissemination, developing transparency and trust between governments and citizens. In light of these benefits, it is imperative to learn the antecedents and underlying mechanisms for this to maintain and enhance engagement.

Objective: The aim of this study is to determine the factors and influencing mechanisms related to citizen engagement with the TikTok account of the National Health Commission of China during the COVID-19 pandemic.

Methods: Using a web crawler, 355 short videos were collected from the Healthy China account on TikTok (with more than 3 million followers throughout China), covering the period from January 21, 2020, to April 25, 2020. The title and video length, as well as the number of likes, shares, and comments were collected for each video. After classifying them using content analysis, a series of negative binomial regression analyses were completed.

Results: Among the 355 videos, 154 (43.4%) related to guidance for clinicians, patients, and ordinary citizens, followed by information concerning the government's handling of the pandemic (n=100, 28.2%), the latest news about COVID-19 (n=61, 17.2%), and appreciation toward frontline emergency services (n=40, 11.3%). Video length, titles, dialogic loop, and content type all influenced the level of citizen engagement. Specifically, video length was negatively associated with the number of likes (incidence rate ratio [IRR]=0.19, P<.001) and comments (IRR=0.39, P<.001). Title length was positively related to the number of shares (IRR=24.25, P=.01), likes (IRR=8.50, P=.03), and comments (IRR=7.85, P=.02). Dialogic loop negatively predicted the number of shares (IRR=0.56, P=.03). In comparison to appreciative information, information about the government's handling of the situation (IRR=5.16, P<.001) and guidelines information (IRR=7.31, P<.001) were positively correlated with the number of shares, while the latest news was negatively related to the number of likes received (IRR=0.46, P=.004). More importantly, the relationship between predictors and citizen engagement was moderated by the emotional valence of video titles. Longer videos with positive titles received a higher number of likes (IRR=21.72, P=.04) and comments (IRR=10.14, P=.047). Furthermore, for short videos related to government handling of the pandemic (IRR=14.48, P=.04) and guidance for stakeholders (IRR=7.59, P=.04), positive titles received a greater number of shares. Videos related to the latest news (IRR=66.69, P=.04) received more likes if the video title displayed higher levels of positive emotion.

Conclusions: During the COVID-19 pandemic, videos were frequently published on government social media platforms. Video length, title, dialogic loop, and content type significantly influenced the level of citizen engagement. These relationships were moderated by the emotional valence of the video's title. Our findings have implications for maintaining and enhancing citizen engagement via government social media.
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http://dx.doi.org/10.2196/21463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864626PMC
February 2021

Enhanced Photovoltaic Efficiency via Control of Self-Assembly in Cyanopyridone-Based Oligothiophene Donors.

J Phys Chem Lett 2021 Jan 13;12(2):919-924. Epub 2021 Jan 13.

Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.

The optoelectronic properties of functional π-conjugated organic materials are affected by their ability to self-assemble within thin films of devices. There are limited reports that demonstrate the positive impact of self-assembly on the photovoltaic performance of organic solar cells. Here, we demonstrate that hydrogen-bonded supramolecular arrays of a cyanopyridone-based oligothiophene donor, CP6, show notable improvement in photovoltaic performance upon self-assembly into a nanofibrous network. The honeycomb-like blend network exhibited higher hole mobility, leading to efficient charge generation and transport. The photovoltaic performance of CP6 was superior to that of two structural analogues, CP5 and CP1, and was attributed to the enhanced capability of CP6 to self-assemble into a film morphology favorable for BHJ devices. The BHJ devices comprising CP6 and the conventional fullerene acceptor (PCBM) exhibited an efficiency of 7.26%, which is greater than that of CP5 (5.19%) and CP1 (3.11%) and is among the best-performing, cyanopyridone-based oligothiophene donors described to date.
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http://dx.doi.org/10.1021/acs.jpclett.0c03526DOI Listing
January 2021

Properties and dynamics of meron topological spin textures in the two-dimensional magnet CrCl.

Nat Commun 2021 Jan 8;12(1):185. Epub 2021 Jan 8.

Institute for Condensed Matter Physics and Complex Systems, School of Physics and Astronomy, The University of Edinburgh, Edinburgh, EH9 3FD, UK.

Merons are nontrivial topological spin textures highly relevant for many phenomena in solid state physics. Despite their importance, direct observation of such vortex quasiparticles is scarce and has been limited to a few complex materials. Here, we show the emergence of merons and antimerons in recently discovered two-dimensional (2D) CrCl at zero magnetic field. We show their entire evolution from pair creation, their diffusion over metastable domain walls, and collision leading to large magnetic monodomains. Both quasiparticles are stabilized spontaneously during cooling at regions where in-plane magnetic frustration takes place. Their dynamics is determined by the interplay between the strong in-plane dipolar interactions and the weak out-of-plane magnetic anisotropy stabilising a vortex core within a radius of 8-10 nm. Our results push the boundary to what is currently known about non-trivial spin structures in 2D magnets and open exciting opportunities to control magnetic domains via topological quasiparticles.
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http://dx.doi.org/10.1038/s41467-020-20497-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794561PMC
January 2021

Quantum Rescaling, Domain Metastability, and Hybrid Domain-Walls in 2D CrI Magnets.

Adv Mater 2021 Feb 21;33(5):e2004138. Epub 2020 Dec 21.

Institute for Condensed Matter Physics and Complex Systems, School of Physics and Astronomy, The University of Edinburgh, Edinburgh, EH9 3FD, UK.

Higher-order exchange interactions and quantum effects are widely known to play an important role in describing the properties of low-dimensional magnetic compounds. Here, the recently discovered 2D van der Waals (vdW) CrI is identified as a quantum non-Heisenberg material with properties far beyond an Ising magnet as initially assumed. It is found that biquadratic exchange interactions are essential to quantitatively describe the magnetism of CrI but quantum rescaling corrections are required to reproduce its thermal properties. The quantum nature of the heat bath represented by discrete electron-spin and phonon-spin scattering processes induces the formation of spin fluctuations in the low-temperature regime. These fluctuations induce the formation of metastable magnetic domains evolving into a single macroscopic magnetization or even a monodomain over surface areas of a few micrometers. Such domains display hybrid characteristics of Néel and Bloch types with a narrow domain wall width in the range of 3-5 nm. Similar behavior is expected for the majority of 2D vdW magnets where higher-order exchange interactions are appreciable.
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http://dx.doi.org/10.1002/adma.202004138DOI Listing
February 2021

Response to "Comment on Acute Kidney Injury after Esophageal Cancer Surgery: Incidence, Risk Factors, and Impact on Oncologic Outcomes".

Ann Surg 2020 Nov 17. Epub 2020 Nov 17.

National Center for Esophageal and Gastric Cancer, Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St. James's Hospital, Dublin 8, Ireland National Center for Esophageal and Gastric Cancer, Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St. James's Hospital, Dublin 8, Ireland National Center for Esophageal and Gastric Cancer, Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St. James's Hospital, Dublin 8, Ireland Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital, Birmingham, UK Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital, Birmingham, UK National Center for Esophageal and Gastric Cancer, Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St. James's Hospital, Dublin 8, Ireland National Center for Esophageal and Gastric Cancer, Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St. James's Hospital, Dublin 8, Ireland National Center for Esophageal and Gastric Cancer, Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St. James's Hospital, Dublin 8, Ireland Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital, Birmingham, UK Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK National Center for Esophageal and Gastric Cancer, Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St. James's Hospital, Dublin 8, Ireland.

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http://dx.doi.org/10.1097/SLA.0000000000004609DOI Listing
November 2020

Concerns Expressed by Chinese Social Media Users During the COVID-19 Pandemic: Content Analysis of Sina Weibo Microblogging Data.

J Med Internet Res 2020 11 26;22(11):e22152. Epub 2020 Nov 26.

School of Political Science and Public Administration, Wuhan University, Wuhan, China.

Background: The COVID-19 pandemic has created a global health crisis that is affecting economies and societies worldwide. During times of uncertainty and unexpected change, people have turned to social media platforms as communication tools and primary information sources. Platforms such as Twitter and Sina Weibo have allowed communities to share discussion and emotional support; they also play important roles for individuals, governments, and organizations in exchanging information and expressing opinions. However, research that studies the main concerns expressed by social media users during the pandemic is limited.

Objective: The aim of this study was to examine the main concerns raised and discussed by citizens on Sina Weibo, the largest social media platform in China, during the COVID-19 pandemic.

Methods: We used a web crawler tool and a set of predefined search terms (New Coronavirus Pneumonia, New Coronavirus, and COVID-19) to investigate concerns raised by Sina Weibo users. Textual information and metadata (number of likes, comments, retweets, publishing time, and publishing location) of microblog posts published between December 1, 2019, and July 32, 2020, were collected. After segmenting the words of the collected text, we used a topic modeling technique, latent Dirichlet allocation (LDA), to identify the most common topics posted by users. We analyzed the emotional tendencies of the topics, calculated the proportional distribution of the topics, performed user behavior analysis on the topics using data collected from the number of likes, comments, and retweets, and studied the changes in user concerns and differences in participation between citizens living in different regions of mainland China.

Results: Based on the 203,191 eligible microblog posts collected, we identified 17 topics and grouped them into 8 themes. These topics were pandemic statistics, domestic epidemic, epidemics in other countries worldwide, COVID-19 treatments, medical resources, economic shock, quarantine and investigation, patients' outcry for help, work and production resumption, psychological influence, joint prevention and control, material donation, epidemics in neighboring countries, vaccine development, fueling and saluting antiepidemic action, detection, and study resumption. The mean sentiment was positive for 11 topics and negative for 6 topics. The topic with the highest mean of retweets was domestic epidemic, while the topic with the highest mean of likes was quarantine and investigation.

Conclusions: Concerns expressed by social media users are highly correlated with the evolution of the global pandemic. During the COVID-19 pandemic, social media has provided a platform for Chinese government departments and organizations to better understand public concerns and demands. Similarly, social media has provided channels to disseminate information about epidemic prevention and has influenced public attitudes and behaviors. Government departments, especially those related to health, can create appropriate policies in a timely manner through monitoring social media platforms to guide public opinion and behavior during epidemics.
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http://dx.doi.org/10.2196/22152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695542PMC
November 2020

Truncating the Pekeris problem.

Authors:
Richard B Evans

J Acoust Soc Am 2020 Sep;148(3):1507

99F Hugo Road, North Stonington, Connecticut 06359, USA.

The exact expression for the difference between the acoustic field in an attenuating Pekeris waveguide and the corresponding truncated waveguide is presented. The derivation replaces an earlier version [Evans, J. Acoust. Soc. Am. 74, 193-194 (1983)] that yielded only an approximate estimate of the same difference. The theoretical simplification resulting from the finite truncation is stressed, in contrast to the infinite half-space.
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http://dx.doi.org/10.1121/10.0001961DOI Listing
September 2020

Peri-operative Outcomes and Survival Following Palliative Gastrectomy for Gastric Cancer: a Systematic Review and Meta-analysis.

J Gastrointest Cancer 2021 Mar 22;52(1):41-56. Epub 2020 Sep 22.

College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Background: Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and bleeding.

Methods: We conducted a systematic review of the literature for all papers describing palliative resections for gastric cancer and reporting peri-operative or survival outcomes. Data from peri-operative and survival outcomes were meta-analysed using random effects modelling. Survival data from patients undergoing palliative resections, non-resective surgery and palliative chemotherapy were also combined. This study was registered with the PROSPERO database (CRD42019159136).

Results: One hundred and twenty-eight papers which included 58,675 patients contributed data. At 1 year, there was a significantly improved survival in patients who underwent palliative gastrectomy when compared to non-resectional surgery and no treatment. At 2 years following treatment, palliative gastrectomy was associated with significantly improved survival compared to chemotherapy only; however, there was no significant improvement in survival compared to patients who underwent non-resectional surgery after 1 year. Palliative resections were associated with higher rates of overall complications versus non-resectional surgery (OR 2.14; 95% CI, 1.34, 3.46; p < 0.001). However, palliative resections were associated with similar peri-operative mortality rates to non-resectional surgery.

Conclusion: Palliative gastrectomy is associated with a small improvement in survival at 1 year when compared to non-resectional surgery and chemotherapy. However, at 2 and 3 years following treatment, survival benefits are less clear. Any survival benefits come at the expense of increased major and overall complications.
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http://dx.doi.org/10.1007/s12029-020-00519-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900337PMC
March 2021

Development of a Physiological Age-Grading System for Nezara viridula (Hemiptera: Pentatomidae).

J Insect Sci 2020 Aug;20(5)

USDA-ARS National Biological Control Laboratory, Stoneville, MS.

The southern green stink bug (SGSB), Nezara viridula (L.), is an important agricultural pest in the United States. Limited information is available on the morphology of the female's reproductive system in relation to morphological changes associated with the number of eggs produced and egg masses oviposited. The ability to assess reproductive health and reproductive status based on ovarian morphology (i.e., physiological age-grading) can be an important tool for evaluating field populations and laboratory colonies intended for the application of different management strategies and experimental trials. Thus, the goal of this study was to develop a physiological age-grading system for SGSB. Females aged from 0 to 79 d chronologically randomly selected from laboratory colonies and dissected to assess ovarian morphology. Specific morphological differences in ovarian structures including differentiation of the ovarioles, deposition of yolk in the most proximal follicle, quantity and appearance of follicular relics, expansion of the lateral oviducts, and number of developing follicles per ovariole were related to chronological age, the number of eggs produced and number of egg masses. Based on specific combinations of these morphological characteristics, the continuum of ovarian development was divided into three nulliparous (i.e., 'no eggs'; N1, N2, and N3) and three parous stages (i.e., 'with eggs'; P1, P2, and P3). Direct relationships were noted between number of eggs produced and physiological age with over 7-fold higher number of eggs and 14-fold higher number of egg masses associated with the P2 and P3 stages, respectively.
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http://dx.doi.org/10.1093/jisesa/ieaa092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494182PMC
August 2020

Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial.

Lancet 2020 Oct 5;396(10259):1353-1361. Epub 2020 Sep 5.

Department of Anaesthesia and Intensive Care, Royal Papworth Hospital, Cambridge, UK.

Background: Preoperative anaemia affects a high proportion of patients undergoing major elective surgery and is associated with poor outcomes. We aimed to test the hypothesis that intravenous iron given to anaemic patients before major open elective abdominal surgery would correct anaemia, reduce the need for blood transfusions, and improve patient outcomes.

Methods: In a double-blind, parallel-group randomised trial, we recruited adult participants identified with anaemia at preoperative hospital visits before elective major open abdominal surgery at 46 UK tertiary care centres. Anaemia was defined as haemoglobin less than 130 g/L for men and 120 g/L for women. We randomly allocated participants (1:1) via a secure web-based service to receive intravenous iron or placebo 10-42 days before surgery. Intravenous iron was administered as a single 1000 mg dose of ferric carboxymaltose in 100 mL normal saline, and placebo was 100 mL normal saline, both given as an infusion over 15 min. Unblinded study personnel prepared and administered the study drug; participants and other clinical and research staff were blinded to treatment allocation. Coprimary endpoints were risk of the composite outcome of blood transfusion or death, and number of blood transfusions from randomisation to 30 days postoperatively. The primary analysis included all randomly assigned patients with data available for the primary endpoints; safety analysis included all randomly assigned patients according to the treatment received. This study is registered, ISRCTN67322816, and is closed to new participants.

Findings: Of 487 participants randomly assigned to placebo (n=243) or intravenous iron (n=244) between Jan 6, 2014, and Sept 28, 2018, complete data for the primary endpoints were available for 474 (97%) individuals. Death or blood transfusion occurred in 67 (28%) of the 237 patients in the placebo group and 69 (29%) of the 237 patients in the intravenous iron group (risk ratio 1·03, 95% CI 0·78-1·37; p=0·84). There were 111 blood transfusions in the placebo group and 105 in the intravenous iron group (rate ratio 0·98, 95% CI 0·68-1·43; p=0·93). There were no significant differences between the two groups for any of the prespecified safety endpoints.

Interpretation: Preoperative intravenous iron was not superior to placebo to reduce need for blood transfusion when administered to patients with anaemia 10-42 days before elective major abdominal surgery.

Funding: UK National Institute of Health Research Health Technology Assessment Program.
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http://dx.doi.org/10.1016/S0140-6736(20)31539-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581899PMC
October 2020

Combined Porogen Leaching and Emulsion Templating to produce Bone Tissue Engineering Scaffolds.

Int J Bioprint 2020 30;6(2):265. Epub 2020 Apr 30.

Department of Materials Science and Engineering, INSIGNEO Institute for in silico Medicine, University of Sheffield, UK.

Bone has a hierarchy of porosity that is often overlooked when creating tissue engineering scaffolds where pore sizes are typically confined to a single order of magnitude. High internal phase emulsion (HIPE) templating produces polymerized HIPEs (polyHIPEs): highly interconnected porous polymers which have two length scales of porosity covering the 1-100 μm range. However, additional larger scales of porosity cannot be introduced in the standard emulsion formulation. Researchers have previously overcome this by additively manufacturing emulsions; fabricating highly microporous struts into complex macroporous geometries. This is time consuming and expensive; therefore, here we assessed the feasibility of combining porogen leaching with emulsion templating to introduce additional macroporosity. Alginate beads between 275 and 780 μm were incorporated into the emulsion at 0, 50, and 100 wt%. Once polymerized, alginate was dissolved leaving highly porous polyHIPE scaffolds with added macroporosity. The compressive modulus of the scaffolds decreased as alginate porogen content increased. Cellular performance was assessed using MLO-A5 post-osteoblasts. Seeding efficiency was significantly higher and mineralized matrix deposition was more uniformly deposited throughout porogen leached scaffolds compared to plain polyHIPEs. Deep cell infiltration only occurred in porogen leached scaffolds as detected by histology and lightsheet microscopy. This study reveals a quick, low cost and simple method of producing multiscale porosity scaffolds for tissue engineering.
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http://dx.doi.org/10.18063/ijb.v6i2.265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415854PMC
April 2020
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